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Influence of neonatal estrogens on rat prostate development
G S Prins1, L Birch, H Habermann
1Department of Urology, University of Illinois at Chicago, 60612, USA.
Reproduction, Fertility, and Development
|January 22, 2002
Summary
Neonatal estrogen exposure permanently alters prostate development in rodents, leading to cellular defects and increased disease risk with aging. These changes involve altered gene expression and receptor signaling, predisposing the prostate to neoplasia.
Area of Science:
- Developmental biology
- Endocrinology
- Urology
Background:
- Early-life exposure to estrogens can permanently affect prostate development.
- Neonatal imprinting by estrogens leads to prostate abnormalities and increased disease incidence later in life.
Purpose of the Study:
- To investigate how early estrogen exposure permanently alters prostate growth, function, and susceptibility to neoplasia.
- To examine the effects of estrogens on prostatic steroid receptors and key developmental genes.
Main Methods:
- Rodent models exposed to estrogens during early development.
- Analysis of prostatic steroid receptors (androgen, estrogen alpha/beta, retinoic acid).
- Examination of cell-cell communication molecules (TGFbeta, gap junctions, cadherins) and developmental genes (Hox-13, Nkx3.1).
Main Results:
- Estrogen exposure caused permanent alterations in steroid receptor expression, including androgen receptors and estrogen receptors alpha (ERalpha).
- Disruptions in TGFbeta signaling, gap junction connexins, and epithelial cadherin were observed.
- Altered expression of developmental genes (Hox-13, Nkx3.1) occurred, with extended hoxa-13, reduced hoxd-13, suppressed hoxb-13, and transient Nkx3.1 decrease.
Conclusions:
- Estrogen imprinting, mediated by stromal ERalpha, alters steroid receptor expression and disrupts normal androgen-driven prostate development.
- Prostate development in estrogenized animals is regulated by alternate steroids, leading to disrupted gene expression patterns.
- These molecular and cellular changes initiated early in life permanently impair prostate differentiation and predispose the gland to aging-associated neoplasia.